ALTERATION OF GLYCOSYLATION RENDERS HIV SENSITIVE TO INACTIVATION BY NORMAL HUMAN SERUM

Retroviruses from various mammalian species, excluding humans, are eff ectively inactivated in normal human serum (NHS). Recent studies have shown that NHS inactivation of retroviruses occurs through natural Ab recognition of a terminal glycosidic moiety on the viral envelope that is acquired during replication in the host cell. This carbohydrate st ructure (the alpha-galactosyl epitope) is expressed on the cells of mo st mammals, with the exception of humans and other Old World primates, In this study, NHS sensitivity of HIV was assessed following viral pr opagation in human cells that were manipulated to express the alpha-ga lactosyl epitope. HUT-78 cells were transduced with an exogenous alpha -1-3-galactosyl transferase gene, which codes for the terminal glycosy l transferase responsible for generation of the alpha-galactosyl epito pe. The transduced HUT-78 cells expressed high levels of the alpha-gal actosyl epitope on their membrane surface, rendering them sensitive to killing in NHS. Similarly, HIV passaged through these cells acquired the alpha-galactosyl epitope in association with the envelope glycopro tein gp120 and was also effectively inactivated in NHS. Viral inactiva tion was abolished by the addition of a synthetic disaccharide that co ntains the alpha-galactosyl epitope, indicating that virolysis is medi ated by anti-alpha-galactosyl natural Ab. These results demonstrate th at, like other retroviruses bearing the alpha-galactosyl epitope, HIV modified to express this epitope is inactivated in NHS. Furthermore, t hese data suggest that expression of the alpha-galactosyl epitope on t he surface of Viruses may have implications in the interspecies transm ission of such viruses to humans.